This project will examine whether (and how) features of actively contracting cardiac muscle (e.g., systolic stress-strain relations, force-interval relations can be quantitatively inferred from measurements in the intact left ventricle. Such inferences would help to evaluate the status of myocardial fiber functioning from measurements in intact hearts (potentially, even in the clinical setting). Our specific aims are: 1) to compare average fiber stress and average strain derived from ventricular pressure and volume measurements to the simultaneously and directly measured stress and strain in an in situ papillary muscle from the same isolated heart during ejection and in isovolumic contractions; 2) examine the distribution (how homogeneous?) of muscle fiber shortening and end-systolic sarcomere lengths in beating ventricles; 3) compare the papillary muscle to the left ventricle with regard to simultaneously measured descriptive characteristics of the force-interval relation [e.g., recirculation fraction, and resititution of mechanical contractility and action potential with time following a beat]; 4) examine the effect of factors [such as heart rate, unsteady pacing, catecholamine, and calcium antagonists] on the force-interval relation in both the in situ muscle and the ventricle. We will use an isolated, supported canine heart preparation to study these questions. The heart is instrumented with 1) a balloon in the left ventricle to control chamber volume, 2) a linear displacement motor to control the length of a right-ventricular papillary muscle, 3) a pair of sonomicrometer crystals to measure muscle length, and 4) a newly developed contact electrode that measures monophasic action potentials. Pressure in the ventricle and force exerted by the muscle are measured by suitable transducers. A unique combination of physiologic and engineering skills has allowed us to develop this highly controlled yet physiologically viable preparation. To study the patterns of sarcomere lengths and shortening in the beating heart, we will combine radiological and histological approaches. Small beads inserted into the myocardium will be tracked via biplane cineradiography and an automated marker-locating system. The pattern of strain in several myocardial layers will be observed throughout the cardiac cycle. To relate this pattern to muscle fiber motion, we will calibrate with respect to fiber angles and sarcomere lengths measured histologically post mortem.